%0 Journal Article
%T Differential expression of copper-associated and oxidative stress related proteins in a new variant of copper toxicosis in Doberman pinschers
%A Bart Spee
%A Paul JJ Mandigers
%A Brigitte Arends
%A Peter Bode
%A Ted SGAM van den Ingh
%A Gaby Hoffmann
%A Jan Rothuizen
%A Louis C Penning
%J Comparative Hepatology
%D 2005
%I BioMed Central
%R 10.1186/1476-5926-4-3
%X We used quantitative real-time PCR to determine differentially expressed genes within a target panel, investigating different groups ranging from copper-associated subclinical hepatitis (CASH) to a clinical chronic hepatitis with high hepatic copper concentrations (Doberman hepatitis, DH). Furthermore, a non-copper associated subclinical hepatitis group (N-CASH) with normal hepatic copper concentrations was added as a control. Most mRNA levels of proteins involved in copper binding, transport, and excretion were around control values in the N-CASH and CASH group. In contrast, many of these (including ATP7A, ATP7B, ceruloplasmin, and metallothionein) were significantly reduced in the DH group. Measurements on defences against oxidative stress showed a decrease in gene-expression of superoxide dismutase 1 and catalase in both groups with high copper. Moreover, the anti-oxidative glutathione molecule was clearly reduced in the DH group.In the DH group the expression of gene products involved in copper efflux was significantly reduced, which might explain the high hepatic copper levels in this disease. ROS defences were most likely impaired in the CASH and DH group. Overall, this study describes a new variant of primary copper toxicosis and could provide a molecular basis for equating future treatments in dog and in man.Copper is an imperative molecule in life; in contradiction, however, it is highly toxic [1]. Like zinc, iron, and selenium, copper is an essential trace element in diets and is required for the activity of a number of physiologically important enzymes [2]. Cells have highly specialized and complex systems for maintaining intracellular copper concentrations [3]. If this balance is disturbed, excess copper can induce oxidative stress that could lead to chronic inflammation [4,5]. Copper induced hepatitis has been described both in humans (Wilson's disease) as well as in dogs. There are several non-human models of copper toxicosis models, such as the Long-E
%U http://www.comparative-hepatology.com/content/4/1/3